FDA: Improper use of hydroxychloroquine, chloroquine for COVID-19 may increase risk for arrhythmias, death
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The FDA issued a safety alert warning health care professionals and patients to avoid the use of hydroxychloroquine and chloroquine outside of hospital or clinical trial settings due to potential increased risk for serious heart-related adverse events and death.
The drugs, which can be used to treat hospitalized patients with COVID-19, may lead to adverse events including ventricular tachycardia, QT interval prolongation, ventricular fibrillation and death in some cases, according to a MedWatch alert from the FDA.
Comments from President Trump on hydroxychloroquine and chloroquine for the treatment of COVID-19 have led to a surge in the demand for these drugs despite the lack of clinical trial results. The agency recently authorized the temporary use of hydroxychloroquine and chloroquine for the treatment of hospitalized patients with COVID-19 through an emergency use authorization despite the drugs’ having several adverse effects including life-threatening arrhythmias. The FDA is reviewing the safety of the drugs’ use outside hospital and clinical trial settings, according to the alert.
According to the alert, case reports have documented heart-related problems, particularly arrhythmias, in patients taking hydroxychloroquine or chloroquine alone or combined with azithromycin or other QT-prolonging medications. Earlier this month, the American Heart Association, the American College of Cardiology and the Heart Rhythm Society issued a guidance on the use of hydroxychloroquine and azithromycin, recommending against their concomitant use in patients with baseline congenital long QT syndrome or a QT of at least 500 milliseconds and encouraging any patients prescribed both to have their cardiac rhythm and QT interval monitored.
The FDA alert noted that hydroxychloroquine and chloroquine should be used with caution in patients with known heart and kidney disease, as they may be at elevated risk for the cardiac adverse effects.
The FDA recommended that patients currently taking hydroxychloroquine and chloroquine for the treatment of autoimmune conditions or malaria should continue taking them as prescribed, as the benefits outweigh the risks at recommended doses. These patients should not stop taking them without consulting their health care provider, according to the alert.
“Be aware that there are no proven treatments for COVID-19 and no vaccine,” the FDA stated in the alert. “If you are receiving hydroxychloroquine or chloroquine for COVID-19 and experience irregular heartbeats, dizziness or fainting, seek medical attention right away by calling 911.”
The alert also instructed consumers not to buy these medicines from online pharmacies without a prescription. Consumers are also instructed not to take hydroxychloroquine or chloroquine if it has not been prescribed to them by a health care provider, as death and serious poisoning have been reported with chloroquine products that are not intended for human consumption.
The FDA recommended health professionals evaluate and monitor their patients who are taking hydroxychloroquine and chloroquine as per the emergency use authorization. Several items that should be monitored include electrolytes, ECG, hepatic tests and renal function.
Hydroxychloroquine and chloroquine have been FDA approved for the treatment or prevention of malaria. In addition, hydroxychloroquine has been approved by the FDA to treat patients with autoimmune conditions including systemic lupus erythematosus in adults, chronic discoid lupus erythematosus and rheumatoid arthritis.
Perspective
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Douglas Esberg, MD, FACC, FHRS
For both medical professionals and the general public, there is a current thirst for knowledge and any treatment that could potentially ameliorate this disease. In addition, there has been a massive amount of conflicting information coming from traditional media, various government agencies and alternative media sources. Much of this information (and misinformation) has led to use of medications with little or no proven benefit.
It was incumbent on the FDA to come out with a clear statement related to the known risks and potential benefits of medications that are being used to treat patients with COVID-19. Both hydroxychloroquine and azithromycin are being used, and are frequently being used in combination. While the benefit of this therapy is not well-known, the CV risks are well-established. It was appropriate for the FDA to give a clear warning about the risk of combination therapy with these two medications related to QT prolongation and potential arrhythmias.
It is also the position of the FDA to give sound scientific guidance to those of us in the medical community. Given the strong support for this unproven therapy from President Trump, there is serious concern that overuse of hydroxychloroquine will lead to drug shortages (which are already being seen) or unnecessary risks to patients. I applaud the FDA for making an attempt to remain scientific- and evidence-based in an era where even treating life-threatening illness in a pandemic has become a partisan political issue.
The short answer to whether these drugs cause serious heart-related adverse events is no. We do know that both hydroxychloroquine and azithromycin have QT-prolonging effects and those effects are additive. In certain susceptible individuals, this could lead to significant QT prolongation and ventricular arrhythmias.
On the other hand, there is much we are still learning about COVID-19 infection. There are many patients with a direct myocardial effect from the virus. It is possible that the virus has a direct membrane effect leading to rhythm instability. There are some patients who develop a myocarditis that can range from subclinical to fulminant. These patients are likely to be at higher risk for ventricular arrhythmias as well. There are still other patients who develop vascular abnormalities and thrombosis which could lead to myocardial ischemia and a propensity towards ventricular arrhythmias. The science on this is evolving quickly and is not fully established at this point.
The advice that cardiologists should give is variable depending on what medications the patient is on already. Depending on their type of CVD, they may already be on a QT-prolonging medication. In this case, I would avoid the combination of hydroxychloroquine and azithromycin unless the patient was being monitored in the hospital. Even with inpatient monitoring, I am frequently discontinuing QT-prolonging medications while the patient is being offered therapy with hydroxychloroquine and azithromycin.
If either one of these two medications is being given individually, some form of monitoring is still reasonable. Frequent ECGs, mobile cardiac outpatient telemetry or inpatient monitoring are all reasonable depending on the clinical situation. If a patient is not on a QT-prolonging medication, the mere fact that they have other CVD is concerning, but would not alter my suggestion for treatment with hydroxychloroquine or azithromycin. These medications should be given with caution and with an understanding of their limited benefit and potential risk.
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